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Normal rat oral keratinocytes have been transformed with the carcinogen 4-nitroquinoline -oxide (4NQO) . The morphology, growth characteristics, ability to grow without anchorage and tumorigenicity in athymic mice was examined in 12 selected cell lines. Each of the lines could be assigned to one of two general groups. The first group of cell lines although showing some morphological signs of transformation and the ability to be subcultured beyond passage 15 were not anchorage independent or able to form tumours in athymic mice. The second group of cell linesshowed distinct signs of morphological transformation, could be serially subcultured without 3T3 feeder cells, were anchorage independent and tumorigenic in athymic mice. Anchorage independence was more common at higher passages and with increased 4NQO treatment and correlated well with a decreased reliance on 3T3 feeder cell support. The anchorage-independent phenotype was dosely associated with the ability to form tumours in athymic mice. This same sequence of phenotypic changes has been demonstrated in rat oral keratinocytes after 4NQO treatment indicating that during carcinogenesis, cell populations progress through the same stages whether proliferation occurs or . There is some evidence to suggest, however, that the time interval between stages may be altered whencarcinogenesi.s takes place . [ABSTRACT FROM PUBLISHER]

An in model of oral epithelial carcinogenesis in rats has been established successfully in cell culture. Oral carcinomas of the tongue and palate were induced in Sprague-Dawley male rats by painting their palates three times weekly for 7 – 8 months with 0.5% (w/v) 4-nitroquinoline--oxide. Oral keratinocytes from malignant and untreated control tissues were cultivated using 3T3 fibroblast support. Both the normal and mahgnant cells stained positively with an anti-human keratin polydonal antibody but mahgnant keratinocytes were heterogeneous with regard to cell size, shape and intercellular packing, unlike the regular organization of the normal cultures. Mahgnant keratinocyte cultures differed markedly from their normal counterparts by an increase in their growth rate, the capacity for serial cultivation to the 25th passage (to date) and independence of 3T3 fibroblast support. In contrast, cultures established from healthy tissue showed signs of senescence usually by passage 4 and were totally reliant on 3T3 fibroblast support for growth. Malignant keratinocytes expressed anchorage independence when cultured in a semi-solid medium and gave rise to tumour formation in athymic mice. The development of this specialized cell culture system substantially increases the potential of the rat 4NQO model to investigate the pathogenesis of oral squamous cell carcinomas. [ABSTRACT FROM PUBLISHER]